Project 1, The Microbial Etiology of Nongonococcal Urethritis (NGU) will comprehensively evaluate the microbial etiology of the most common urethritis syndrome in North America for the first time in over two decades. The project will utilize state of the art, maximally sensitive assays to detect putative agents of NGU in randomly selected, high risk men attending a STD Clinic over a four-year period. Three complimentary strategies will be utilized to determine which agents and in what proportion currently cause for NGU in men. First, a battery of microbial detection tests will be performed on men with NGU and on comparison groups of men with gonococcal urethritis and without urethritis. Each man will be tested by cell culture for Chlamydia trachomatis and herpes simplex virus, by culture for Ureaplasma urealyticum, Trichomonas vaginalis, Mycoplasma genitalium and "traditional" bacterial urinary tract pathogens such as Staphylococcus saprophyticus and enterococci. In addition, genitourinary specimens from study participants will be tested by PCR for M. genitalium, specific U. urealyticum biotypes, and Herpes simplex virus. Finally, in the final two years of this project, men with culture negative NGU will be evaluated for heretofore unidentified, difficult to cultivate bacteria using 16S rRNA PCR. To compliment these studies, the investigators will also evaluate the transmissibility of M. genitalium and of specific U. urealyticum biotypes to sexual partners to help validate the role of these agents as causal agents in NGU. Finally, by testing participants at enrollment and at 1 month at following enrollment, response to antimicrobial therapy can be evaluated using repeated evaluation for each of the pathogens listed above following therapy or by evaluating persistence of those pathogens in asymptomatic, untreated men. Over the 4 year study period, sufficient men will be enrolled to allow evaluation using multivariate analysis to measure the import of variables likely to modify the distribution of NGU etiologic agents such as age and history of prior urethritis.